Letter to the Editor: Modeling concerns
Authors: Elliot B. Tapper
Journal: Hepatology (2023)

To the editor, Decision-analytic modeling is a powerful tool to extend the impact of clinical research and inform clinical and health policy decisions.1 The recent publication, "Cost effectiveness of MRE vs VCTE in staging fibrosis for non-alcoholic fatty liver disease (NAFLD) patients with advanced fibrosis,"2 sought to extend clinical data regarding noninvasive methods for case identification of NAFLD with advanced fibrosis. The aim of early detection is to intervene and forestall the development of cirrhosis and its complications. However, as long-term studies after baseline elastography are lacking, modeling is needed to connect the early detection data to knowledge of natural history. The limits of method are related to the validity of the inputs and the calibration of the model. In this publication's case, limits relating to the model construction are listed in the Table 1. There are 3 key areas to be addressed. First, as each patient in the model is 50 years old and gains an average of 50 quality-adjusted life-years (QALYs) the average patient in the model lives to 100 years or later. Second, MRE offers marginal (5%) improvements in detection over VCTE, but it provides an incremental survival benefit of 1.23–1.71 QALYs. This is 2-fold greater than that conferred by direct-acting antivirals for hepatitis C (0.56 QALYs).3 It is >6-fold greater than the incremental benefit associated with use of the NAFLD Fibrosis Score alone (0.20 QALYs).4 Third, 2 strategies (VCTE and VCTE+MRE) generate identical costs. TABLE 1 - Areas to address Modeling concerns Assumption concerns Reporting requests ICER table:All strategies resulted in a gain of >49.9 QALY. As all patients began the simulation at age 50 years, this would mean the average patient lived to be >100 years old.The total costs of care for VCTE alone and MRE in addition to VCTE are identical: $392,763 Mortality is modeled by stage of liver disease. Although people with F1/F2 fibrosis have a 0% mortality per cycle, those with F3 have 0.4%, and compensated cirrhosis 4%. This could result in immorality for some patients. To understand the modeling, the authors after requested to describe the life years per arm as well as the incidence of cirrhosis, HCC, and liver transplant per arm MRE was modeled to have 5% greater specificity for advanced fibrosis but resulted in > 1 incremental QALY. This is unlikely given that DAAs provide 0.56 additional QALYs over interferon-based regimens for hepatitis C The prevalence of advanced fibrosis after FIB4 ≥ 2.67 is assumed to be 80%. This would only be accurate if the pretest probability of advanced fibrosis was >20% which is unlikely in the screening setting. The authors are requested to provide the proportion referred for therapy by arm as well as the proportion which reverse their fibrosis by arm Only patients identified as having advanced fibrosis were referred for therapy which was the MOVE! Program of the Veterans Affairs. However, many patients with NAFLD risk factors are referred in standard care Abbreviations: DAA, direct-acting antivirals; ICER, incremental cost-effectiveness ratio; MRE, magnetic resonance elastography; QALY, quality-adjusted life years; VCTE, vibration-controlled transient elastography.